Molecular mechanisms of postoperative atrial fibrillation in patients with obstructive sleep apnea.

Obstructive sleep apnea (OSA) promotes atrial remodeling and fibrosis, providing a substrate for atrial fibrillation (AF). Herein, we investigate the pathophysiological mechanisms of AF in association with OSA in a cohort of cardiac surgery patients. A prospective study including patients undergoing cardiac surgery. Biomarkers reflective of AF pathophysiology (interleukin [IL-6], C-reactive protein [CRP], von Willebrand factor [vWF], N-terminal pro-brain natriuretic peptide [NT-proBNP], high-sensitivity Troponin T [hs-TnT], and Galectin-3 [Gal-3]) was assessed by functional or immunological assays. miRNAs involved in AF were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Using atrial tissue samples, fibrosis was assessed by Masson's trichrome. Connexin 40 and 43 (Cx40; Cx43) were evaluated by immunolabeling. Fifty-six patients (15 with OSA and 41 non-OSA) were included in this hypothesis-generating pilot study. OSA group had a higher incidence of postoperative AF (POAF) (46.7% vs. 19.5%; p = .042), presented an increased risk of POAF (OR 3.61, 95% CI 1.01-12.92), and had significantly higher baseline levels of NT-proBNP (p = .044), vWF (p = .049), Gal-3 (p = .009), IL-6 (p = .002), and CRP (p = .003). This group presented lower levels of miR-21 and miR-208 (both p < .05). Also, lower Cx40 levels in POAF and/or OSA patients (50.0% vs. 81.8%, p = .033) were found. The presence of interstitial fibrosis (according to myocardial collagen by Masson's trichrome) was raised in OSA patients (86.7% vs. 53.7%, p = .024). Several biomarkers and miRNAs involved in inflammation and fibrosis were dysregulated in OSA patients, which together with a higher degree of interstitial fibrosis, altered miRNA, and Cxs expression predisposes to the development of a substrate that increases the AF risk.

Imaging in atrial fibrillation: A way to assess atrial fibrosis and remodeling to assist decision-making.

The 2020 ESC atrial fibrillation (AF) guidelines suggest the novel 4S-AF scheme for the characterization of AF. Imaging techniques could be helpful for this objective in everyday clinical practice, and information derived from these techniques reflects basic aspects of the pathophysiology of AF, which may facilitate treatment decision-making, and optimal management of AF patients. The aim of this review is to provide an overview of the mechanisms associated with atrial fibrosis and to describe imaging techniques that may help the management of AF patients in clinical practice. Transthoracic echocardiography is the most common procedure given its versatility, safety, and simplicity. Transesophageal echocardiography provides higher resolution exploration, and speckle tracking echocardiography can provide incremental functional and prognostic information over conventional echocardiographic parameters. In addition, LA deformation imaging, including LA strain and strain rate, are related to the extent of fibrosis. On the other hand, multidetector-row computed tomography and cardiac magnetic resonance provide higher resolution data and more accurate assessment of the dimensions, structure, and spatial relationships of the LA. Imaging is central when deciding on catheter ablation or cardioversion, and helps in selecting those patients who will really benefit from these procedures. Moreover, imaging enhances the understanding of the underlying mechanisms of atrial remodeling and might assists in refining the risk of stroke, which help to select the best medical therapies/interventions. In summary, evaluation of LA enlargement, LA remodeling and fibrosis with imaging techniques adds clinical and prognostic information and should be assessed as a part of routine comprehensive AF evaluation.

Evidence for a lack of inotropic and chronotropic effects of glucagon and glucagon receptors in the human heart.

BACKGROUND: Glucagon is thought to increase heart rate and contractility by stimulating glucagon receptors and increasing 3',5'-cyclic adenosine monophosphate (cAMP) production in the myocardium. This has been confirmed in animal studies but not in the human heart. The cardiostimulatory effects of glucagon have been correlated with the degree of cardiac dysfunction, as well as with the enzymatic activity of phosphodiesterase (PDE), which hydrolyses cAMP. In this study, the presence of glucagon receptors in the human heart and the inotropic and chronotropic effects of glucagon in samples of failing and nonfailing (NF) human hearts were investigated. METHODS: Concentration‒response curves for glucagon in the absence and presence of the PDE inhibitor IBMX were performed on samples obtained from the right (RA) and left atria (LA), the right (RV) and left ventricles (LV), and the sinoatrial nodes (SNs) of failing and NF human hearts. The expression of glucagon receptors was also investigated. Furthermore, the inotropic and chronotropic effects of glucagon were examined in rat hearts. RESULTS: In tissues obtained from failing and NF human hearts, glucagon did not exert inotropic or chronotropic effects in the absence or presence of IBMX. IBMX (30 µM) induced a marked increase in contractility in NF hearts (RA: 83 ± 28% (n = 5), LA: 80 ± 20% (n = 5), RV: 75 ± 12% (n = 5), and LV: 40 ± 8% (n = 5), weaker inotropic responses in the ventricular myocardium of failing hearts (RV: 25 ± 10% (n = 5) and LV: 10 ± 5% (n = 5) and no inotropic responses in the atrial myocardium of failing hearts. IBMX (30 µM) increased the SN rate in failing and NF human hearts (27.4 ± 3.0 beats min-1, n = 10). In rat hearts, glucagon induced contractile and chronotropic responses, but only contractility was enhanced by 30 µM IBMX (maximal inotropic effect of glucagon 40 ± 8% vs. 75 ± 10%, in the absence or presence of IBMX, n = 5, P < 0.05; maximal chronotropic response 77.7 ± 6.4 beats min-1 vs. 73 ± 11 beats min-1, in the absence or presence of IBMX, n = 5, P > 0.05). Glucagon receptors were not detected in the human heart samples. CONCLUSIONS: Our results conflict with the view that glucagon induces inotropic and chronotropic effects and that glucagon receptors are expressed in the human heart.

Novel insights in the relationship of gut microbiota and coronary artery diseases.

Atherosclerosis is a chronic, progressive, inflammatory disease in the vasculature and is common in both coronary and peripheral arteries. Human beings harbor a complex and dynamic population of microorganisms defined as the microbiota. Importantly, alterations in the bacterial composition (dysbiosis) and the metabolic compounds produced by these bacteria have been associated with the pathogenesis of many inflammatory diseases and infections. There is also a close relationship between intestinal microbiota and cardiovascular diseases. The aim of this review was to analyze how changes in the gut microbiota and their metabolites might affect coronary artery diseases. The most representative groups of bacteria that make up the intestinal microbiota are altered in coronary artery disease patients, resulting in a decrease in Bacteroidetes and an increase in Firmicutes. In relation to metabolites, trimethylamine-N-oxide plays an important role in atherosclerosis and may act as a cardiovascular risk predictor. In addition, the use of probiotics, prebiotics, diet modulation, and fecal transplantation, which may represent alternative treatments for these diseases, is thoroughly discussed. Finally, the role of lipid-lowering treatments is also analyzed as they may affect and alter the gut microbiota and, conversely, gut microbiota diversity could be associated with resistance or sensitivity to these treatments.

Novel biomarkers in Alzheimer's disease using high resolution proteomics and metabolomics: miRNAS, proteins and metabolites.

Alzheimer's disease (AD) is the most common form of dementia. It affects approximately 6% of people over the age of 65 years. It is a clinicopathological, degenerative, chronical and progressive disease that exhibits a deterioration of memory, orientation, speech and other functions. Factors contributing to the pathogenesis of the disease are the presence of extracellular amyloid deposits, called neuritic senile plaques, and fibrillary protein deposits inside neurons, known as neurofibrillary bundles, that appear mainly in the frontal and temporal lobes. AD has a long preclinical latency and is difficult to diagnose and prevent at early stages. Despite the advent of novel high-throughput technologies, it is a great challenge to identify precise biomarkers to understand the progression of the disease and the development of new treatments. In this sense, important knowledge is emerging regarding novel molecular and biological candidates with diagnostic potential, including microRNAs that have a key role in gene repression. On the other hand, proteomic approaches offer a platform for the comprehensive analysis of the whole proteome in a certain physiological time. Proteomic technology investigates protein expression directly and reveals post-translational modifications known to be determinant for many human diseases. Clinically, there is growing evidence for the role of proteomic and metabolomic technologies in AD biomarker discovery. This review discusses the role of several miRNAs identified using genomic technologies, and the importance of novel proteomic and metabolomic approaches to identify new proteins and metabolites that may be useful as biomarkers for monitoring the progression and treatment of AD.

Intestinal microbiota alterations in chronic kidney disease and the influence of dietary components.

In chronic kidney disease, as in many other diseases, dysbiosis of intestinal microbiota has been reported as a disturbance or imbalance of the normal microbiome content that could disrupt the symbiotic relationship between the host and associated microbes, a disruption that can result in diseases. The disruption of gut barrier function allows the translocation of endotoxins and bacterial metabolites to the organism, thus contributing to uremic toxicity, inflammation and progression of chronic kidney disease. Increased intake of some nutrients and different nutritional strategies have been proposed to modulate gut microbiota, thus offering the opportunity for therapeutic interventions modifying the diet, decreasing uremic toxins production, increasing toxin excretion and finally modifying the normal microbiome content. The use of probiotics, prebiotics and low protein diets, among other approaches, could also improve this imbalance and/or decrease permeability of the intestinal barrier. In this review, the link between nutrients, microbiota and uremic toxins with chronic kidney disease progression has been studied thoroughly. Furthermore, this review outlines potential mechanisms of action and efficacy of probiotics, prebiotics and low protein diets as a new chronic kidney disease management tool.

Antithrombotic Therapy in Patients with Peripheral Artery Disease: A Focused Review on Oral Anticoagulation.

Peripheral artery disease (PAD) is a major cause of morbidity and mortality but it is usually underdiagnosed and undertreated. Patients with PAD present dysregulated procoagulant, anticoagulant, and fibrinolytic pathways leading to arterial and venous thrombosis. The risk of several ischemic-related complications could be mitigated with appropriate antithrombotic therapy, which plays a central role in all types of PAD. For years, antiplatelets have been indicated in patients with symptomatic PAD or those who have undergone revascularization. Unfortunately, a non-negligible proportion of patients with PAD will suffer from adverse events during the follow-up, even despite proper medical therapies for the prevention of PAD complications. Thus, there is room for improving clinical outcomes in these patients. Given the implication of both, primary and secondary hemostasis in arterial thrombosis and the pathophysiology of PAD, the combination of antiplatelets and anticoagulants has emerged as a potential antithrombotic alternative to antiplatelets alone. In this narrative review article, we have highlighted the most recent evidence about antithrombotic therapy in PAD patients, with a special focus on oral anticoagulation. Certainly, COMPASS and VOYAGER PAD trials have shown promising results. Thus, rivaroxaban in combination with aspirin seem to reduce cardiovascular outcomes with a similar bleeding risk compared to aspirin alone. Nevertheless, results from real-world studies are needed to confirm these observations, and other trials will provide novel evidence about the safety and efficacy of emerging anticoagulant agents.

Immunoscore: a novel prognostic tool. Association with clinical outcome, response to treatment and survival in several malignancies.

The predictive accuracy of the traditional staging system for cancer, the American Joint Committee on Cancer/Union Internationale Centre le Cancer (AJCC/UICC) classification of malignant tumors, is based on disease progression as a tumor cell-autonomous process, regardless the effects of the host immune response. The natural history of a tumor includes different phases of growth, migration and invasion. During these phases, tumor cells interact with their microenvironment and are influenced by signals from stromal, endothelial, inflammatory and immune cells. Indeed, tumors are often infiltrated by defensive cells such as lymphocytes, macrophages or mast cells and it has been shown extensively that lymphocytes may control cancer outcome, as evidenced in several human malignancies. Increasing evidence suggests that cancer progression is strongly influenced by host immune response, which is represented by immune cell infiltrates. The T-lymphocyte-based immunoscore (IS) has proved to be a prognostic factor in human malignancies such as colon, pancreas and lung cancer, hepatocellular carcinoma, melanoma and even brain metastases. Although the IS was initially established to evaluate the prognosis of stage I/II/III colon cancer patients, its association with clinical outcomes and survival has been shown in other malignancies. The aim of this review is to analyze the association of IS with prognosis, survival and response to therapy in different tumor types.

Alterations of circadian rhythms and their impact on obesity, metabolic syndrome and cardiovascular diseases.

Circadian system is comprised by central circadian pacemaker and several peripheral clocks that receive information from the external environment, synchronizing the circadian clocks. It is widely known that physiology is rhythmic and that the rupture of this rhythmicity can generate serious consequences. Circadian clocks, led by suprachiasmatic nucleus (SCN) in the central nervous system, are the responsible for generating this biological rhythmicity. These clocks are affected by external signals such as light (changes between day and night) and feeding rhythms. In this review, the basic principles of the circadian system and current knowledge of biological clocks are addressed, analyzing the relationship between circadian system, food intake, nutrition, and associated metabolic processes. In addition, the consequences occurring when these systems are not well coordinated with each other, such as the development of cardiovascular and metabolic pathologies, will be thoroughly discussed.

One-year efficacy and safety of prasugrel and ticagrelor in patients with acute coronary syndromes: Results from a prospective and multicentre ACHILLES registry.

BACKGROUND: Prasugrel and ticagrelor have demonstrated higher efficacy than clopidogrel in their main clinical trials for patients with acute coronary syndrome (ACS). However, the long-term prognosis and different clinical characteristics related to the type of antiplatelet prescription in current clinical practice ACS patients have not been analysed in depth. The objective of this study was to analyse the clinical profile of ACS and the efficacy and safety of novel oral P2Y12 inhibitors in current clinical practice patients discharged afterACS. METHODS: We collected data from the ACHILLES registry, and an observational, prospective and multicentre registry of patients discharged after ACS. We analysed baseline characteristics, clinical profile and therapy during ACS admission and compared with the different treatments at discharge. After 1 year of follow-up, ischaemic and major bleeding events were analysed. Multivariate Cox regression analysis and Kaplan Meier curves were also plotted. RESULTS: Of 1717 consecutive patients, 1294 (75.4%) were discharged with a P2Y12 inhibitor without oral anticoagulation. Novel oral P2Y12 inhibitors were indicated in 47%. Patients treated with clopidogrel were elderly (69.1 ± 13.4 vs 60.4 ± 11.5 years; P < .001) and had a higher prevalence of cardiovascular risk factors. GRACE and CRUSADE scores were higher in the clopidogrel than in novel oral P2Y12 inhibitors group (P < .001). After 1 year of follow-up, 64(5.0%/year) patients had a new myocardial infarction, 127(10.0%/year) had a major adverse cardiovascular event (MACE) and 78(6.1%/year) died. Patients treated with clopidogrel had a significantly higher annual rate of cardiovascular mortality, MACE and all-cause mortality (allP < .001) without differences in major bleeding (P = .587) compared with novel oral P2Y12 inhibitors. After multivariate adjustment for the main clinical variables related to adverse prognosis in ACS patients, the discharge with novel oral P2Y12 inhibitors therapy was independently associated with lower risk of all-cause mortality (HR0.49, 95% CI [0.24-0.98], P = .044) and lower risk of MACE (HR0.64, 95% CI [0.41-0.98], P = .044). CONCLUSIONS: In this prospective, observational and current clinical practice ACS registry, the use of novel oral P2Y12 inhibitors was associated with a reduction in adverse events compared with clopidogrel in patients with ACS. Novel oral P2Y12 inhibitors prescription at discharge was independently associated with lower all-cause mortality and MACE without differences in bleeding events. However, clopidogrel remained the most common P2Y12 inhibitor employed for ACS, especially in older and high-risk patients.

Impact of gut microbiota on neurological diseases: Diet composition and novel treatments.

Gut microbiota has significant effects on the structure and function of the enteric and central nervous system including human behaviour and brain regulation. Herein, we analyze the role of this intestinal ecosystem, the effects of dietary changes and the administration of nutritional supplements, such as probiotics, prebiotics, or fecal transplantation in neuropsychiatric disorders. Numerous factors have been highlighted to influence gut microbiota composition, including genetics, health status, mode of birth delivery and environment. However, diet composition and nutritional status has been repeatedly shown to be one of the most critical modifiable factors of this ecosystem. A comprehensively analysis of the microbiome-intestine-brain axis has been performed, including the impact of intestinal bacteria in alterations in the nervous, immune and endocrine systems and their metabolites. Finally, we discuss the latest literature examining the effects of diet composition, nutritional status and microbiota alterations in several neuropsychiatric disorders, such as autism, anxiety, depression, Alzheimer's disease and anorexia nervosa.

The future of nutrition: Nutrigenomics and nutrigenetics in obesity and cardiovascular diseases.

Over time, the relationship between diet and health has aroused great interest, since nutrition can prevent and treat several diseases. It has been demonstrated that general recommendations on macronutrients and micronutrients do not affect to every individual in the same way because diet is an important environmental factor that interacts with genes. Thus, there is a growing necessity of improving a personalized nutrition to treat obesity and associated medical conditions, taking into account the interactions between diet, genes and health. Therefore, the knowledge of the interactions between the genome and nutrients at the molecular level, has led to the advent of nutritional genomics, which involves the sciences of nutrigenomics and nutrigenetics. In this review, we will comprehensively analyze the role of the most important genes associated with two interrelated chronic medical conditions, such as obesity and cardiovascular diseases.

Temporal Changes in Platelet Response in Acute Coronary Syndrome Patients With Prasugrel and Clopidogrel After Stent Implantation.

BACKGROUND: Prasugrel has been shown to provide more potency and less variability than clopidogrel, but its potential temporal variability has not been described.Methods and Results:We conducted a prospective open-label study, evaluating platelet reactivity overtime in acute coronary syndrome (ACS) patients on aspirin and clopidogrel (n=60) or prasugrel (n=61), after a percutaneous coronary intervention (PCI). Blood samples were taken at discharge and at 3 and 6 months. Platelet function tests included VerifyNow (VN-P2Y12), and Multiplate Aggregometry (MEA). By means of VN-P2Y12, prasugrel patients displayed significantly (P<0.001) higher platelet inhibition than clopidogrel patients over time, although there were not significant differences using MEA. Prasugrel patients showed higher platelet inhibition at baseline than at 3 months (59.3±8.1 vs. 105.0±49.2; P<0.001), without significant change at 6 months (107.9±72.0; P=0.919 vs. 3 months). Clopidogrel patients showed a similar trend (160.1±65.1, 184.8±62.7 and 185.0±53.3; baseline vs. 3 months P=0.060; 3 months vs. 6 months P=0.974). High platelet reactivity (HPR) was shown in 16.3% prasugrel patients, with no patient consistently remaining in HPR over time. HPR was detected in 36.6% of the clopidogrel patients, being consistently observed in 15.0% of them. Low platelet reactivity (LPR) was detected in 60.5% prasugrel and 9.8% clopidogrel patients. CONCLUSIONS: Prasugrel patients showed less temporal variation than patients on clopidogrel in terms of HPR. In contrast, higher variability in LPR was detected in prasugrel patients for up to 6 months' follow-up.

Deciphering acute coronary syndrome biomarkers: High-resolution proteomics in platelets, thrombi and microparticles.

Acute coronary syndromes (ACS) encompass unstable angina, non-ST segment elevation myocardial infarction, ST-segment elevation myocardial infarction and sudden cardiac death. They are commonly associated with the presence of vulnerable plaques in the coronary arteries and occur when a thrombus formed from a ruptured atheromatous plaque causes a prolonged occlusion of a coronary artery. The erosion of the vulnerable plaques results in the formation of luminal thrombi secondary to platelet activation and the release of thrombogenic elements within the atherosclerotic lesions. Proteomic approaches offer an unbiased platform for the comprehensive analysis of the whole proteome in a certain physiological time. Although mRNA expression is widely considered to be indicative of protein expression, protein levels are the result of protein synthesis and degradation, and RNA levels are not informative of protein degradation. In contrast, the proteomic technology investigates protein expression directly. This is particularly important in the context of atherosclerosis in which protein degradation is as decisive as protein synthesis. Moreover, proteomics reveals post-translational modifications known to be determinant for many human diseases. Clinically, there is increasing evidence for the role of proteomic technology in biomarker discovery that will provide novel information on the molecular events associated with ACS, and potentially lead to the identification of novel drug targets. In this review, we describe in detail the importance of proteomic approaches to identify new biomarkers associated with ACS from three perspectives: biomarkers associated with platelet metabolism; the study of proteomics of intravascular thrombi; and proteome analysis of membrane microparticles released from activated cells, mostly by platelets.

High-resolution proteomics and metabolomics in thyroid cancer: Deciphering novel biomarkers.

The incidence of thyroid cancer (TC) - the most common endocrine malignancy - has been increasing sharply since the mid-1990s. The rate of TC incidence in both men and women has been faster than any other cancer. Both improved diagnoses (i.e. increased medical surveillance and more sensitive diagnostic tests, such as ultrasound and confirmation via fine-needle aspiration biopsy (FNAB)), and environmental factors detrimental to thyroid health are thought to account for the increased incidence. There are several histological types of thyroid carcinoma including papillary, follicular, medullary, and anaplastic. Determining the type of TC is crucial for prognosis and treatment selection. Unfortunately, approximately 20-30% of patients undergoing FNAB have inconclusive or indeterminate results, leading to unnecessary surgical intervention in 80% of patients with benign nodules. To resolve this diagnostic dilemma, new biomarkers of TC are needed. Proteomic approaches offer an unbiased platform for the comprehensive analysis of the whole proteome. Although mRNA expression is widely considered to be indicative of protein expression, protein levels are the result of protein synthesis and degradation, yet RNA levels are only indicative of protein synthesis. Clinically, there is growing evidence for the role of proteomic and metabolomic technologies in TC biomarker discovery, providing novel information on the molecular events associated with TC, and potentially leading to the identification of novel drug targets. This review thoroughly discusses the importance of novel proteomic and metabolomic approaches to identify new biomarkers for TC.

Anti-inflammatory effects of omega 3 and omega 6 polyunsaturated fatty acids in cardiovascular disease and metabolic syndrome.

A lipid excess produces a systemic inflammation process due to tumor necrosis factor-α, interleukin-6 and C-reactive protein synthesis. Simultaneously, this fat excess promotes the appearance of insulin resistance. All this contributes to the development of atherosclerosis and increases the risk of cardiovascular diseases (CVDs). On the other hand, polyunsaturated fatty acids (PUFAs), especially eicosapentaenoic acid and docosahexaenoic acid (omega 3), and arachidonic acid (omega 6) have shown anti-inflammatory properties. Lately, an inverse relationship between omega-3 fatty acids, inflammation, obesity and CVDs has been demonstrated. To check fatty acids effect, the levels of some inflammation biomarkers have been analyzed. Leptin, adiponectin and resistin represent a group of hormones associated with the development of CVDs, obesity, type 2 diabetes mellitus and insulin resistance and are modified in obese/overweight people comparing to normal weight people. Omega-3 PUFAs have been shown to decrease the production of inflammatory mediators, having a positive effect in obesity and diabetes mellitus type-2. Moreover, they significantly decrease the appearance of CVD risk factors. Regarding omega-6 PUFA, there is controversy whether their effects are pro- or anti-inflammatory. The aim of this manuscript is to provide a comprehensive overview about the role of omega-3 and omega-6 PUFAs in CVDs and metabolic syndrome.

Clinical implications of nonsarcomeric gene polymorphisms in hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is characterized by cardiomyocyte hypertrophy and fibrosis. Although is an autosomal dominant trait, a group of nonsarcomeric genes have been postulated as modifiers of the phenotypic heterogeneity. MATERIAL AND METHODS: We prospectively recruited 168 HCM patients and 136 healthy controls from three referral centres. Patients and controls were clinically stable at entry in the study. Nine polymorphisms previously associated with ventricular remodelling were determined: I/D ACE, AGTR1(A1666C), CYP11B2(C344T), PGC1-α(G482S), COLIA1(G2046T), ADRB1(R389G), NOS3(G894T), RETN(-420C>G) and CALM3(-34T>A). Their potential influence on prognosis, assessed by hospital admissions, and their cause were recorded. RESULTS: The median follow-up time was 49·5 months. Allele and genotype frequencies did not differ between patients and controls. Thirty-six patients (21·5%) required urgent hospitalization (18·5% for heart failure, 22·2% for atrial arrhythmias, 11·1% for ventricular arrhythmias, 29·6% for ischaemic heart disease, 14·8% for stroke and 3·7% for other reasons) with a hospitalization rate of 8·75% per year. Multivariate analysis showed an independent predictive value for noncarriers of polymorphic COL1A1 allele [HR: 2·76(1·26-6·05), P = 0·011] and a trend in homozygous carriers of ADRB1 Arg389 variant [HR: 1·98(0·99-4·02); P = 0·057]. CONCLUSION: Our study suggests that COL1A1 polymorphism (2046G>T) is an independent predictor of prognosis in HCM patients supporting the importance of nonsarcomeric genes on clinical prognosis in HCM.

Platelet reactivity over time in coronary artery disease patients treated with a bioabsorbable everolimus-eluting scaffold.

Everolimus-eluting bioabsorbable scaffolds (BVSs) have exhibited similar long-term clinical outcomes compared to its everolimus-eluting metallic counterparts. However, reports from earlier studies have shown a signal for an increased rate of stent thrombosis. The aim of the current investigation is to describe the platelet reactivity profiles over time in patients treated with everolimus-eluting BVS in comparison to everolimus-eluting metallic stents. This is a pilot study in which patients on aspirin and clopidogrel with at least 1 everolimus-eluting BVS were included (n = 24). Patients with at least 1 everolimus-eluting metallic stent implanted were included as control group (n = 25). Blood samples were taken at time of discharge and at 3- and 6-month follow-up. Platelet function tests included VerifyNow (VN-P2Y12), multiplate aggregometry (MEA), and light transmission aggregometry (LTA). There was no difference in platelet reactivity at discharge, 3- and 6-month visits (unadjusted p = 0.733 and p = 0.582; p = 0.432 and p = 0.899 after adjusting for discharge value platelet reactivity0, respectively) using VN-P2Y12. Similar findings were observed with LTA. However, patients with BVS showed significantly higher platelet reactivity than patients with metallic stents at 3 and 6 months in the crude analysis (p = 0.003) and after adjusting for discharge value (p = 0.013) measured with ADP-MEA. There were no differences in platelet reactivity mediated by the T × A2 pathway between both groups. Finally, there is no statistical difference in high on-clopidogrel platelet reactivity (HPR) rate between both groups. The results of this pilot study suggest that BVS might have different platelet reactivity profiles, and warrants further investigation in dedicated clinical studies.

Familial nonmedullary thyroid cancer: screening, clinical, molecular and genetic findings.

Thyroid cancer, the commonest of endocrine malignancies, continues increasing in incidence being the 5th more prevalent cancer among women in the United States in 2012. Familial thyroid cancer has become a well-recognized, unique, clinical entity in patients with thyroid cancer originating from follicular cells, that is, nonmedullary thyroid carcinoma. Hereditary nonmedullary thyroid cancer may occur as a minor component of familial cancer syndromes (familial adenomatous polyposis, Gardner's syndrome, Cowden's disease, Carney's complex type 1, Werner's syndrome, and papillary renal neoplasia) or as a primary feature (familial nonmedullary thyroid cancer [FNMTC]). Although there is some controversy, some epidemiologic and clinical kindred studies have shown that FNMTC is associated with more aggressive disease than sporadic cases, with higher rates of multicentric tumours, lymph node metastasis, extrathyroidal invasion, and shorter disease-free survival. This way, preventing screening will allow earlier detection, more timely intervention, and hopefully improved outcomes for patients and their families. On the other hand, in the last years, an important number of genetic studies on FNMTC have been published, trying to determine its genetic contribution. However, the genetic inheritance of FNMTC remains unclear; but it is believed to be autosomal dominant with incomplete penetrance and variable expressivity. This paper provides an extensive overview of FNMTC from several points of view. Firstly, the impact of early detection on prognosis, secondly, the management and follow-up of FNMTC patients, and finally, the role of susceptibility loci, microRNAs (miRNAs) and telomerases in recently identified isolated cases of FNMTC.

A comprehensive insight of novel antioxidant therapies for atrial fibrillation management.

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and is associated with decreased quality of life, and increased mortality and morbidity from stroke and thromboembolism. The underlying mechanisms involved in the development of AF have yet to be fully elucidated. However, once initiated, AF tends to self-perpetuate, due to structural and electrical remodeling in the atria. Currently, therapies for AF, such as, antiarrhythmic drugs and catheter ablation, have significant limitations. Antiarrhythmic drugs target one or a few cardiomyocyte ion channels and have considerable pro-arrhythmic and non-cardiac adverse effects. On the other hand, catheter ablation is an expensive treatment associated with measurable complications and its long-term success in management of AF is controversial. Current consensus guidelines recommend ß-blockers, amiodarone, digitalis glycosides and non-dihydropyridine calcium channel antagonists or a combination of them for AF treatment, but bradycardia and heart block may occur as an unwanted effect. On the other hand, antioxidant agents have recently attracted much interest in AF treatment because they have been associated with a reduction in lone AF and post-operative AF, and in some cases, with a decrease in long-term hospitalization time. Moreover, antioxidants can be considered a cheap treatment with reduced side effects. In this review, we will comprehensively review the effects and the mechanisms of action of several antioxidant agents, such as vitamin E, ascorbic acid, carotenoids, statins, omega-3 polyunsaturated fatty acids and N-acetylcysteine.